Maybe it has something to do with the capillaries being closer to the skin when you smoke. Redness reducing drops work as a vasoconstrictor, or they constrict the blood vessels in your eyes to make them less visible. If your eyes arent red to begin with, they have nowhere to be absorbed. Once you smoke, the THC causes the blood vessels to swell, and your eyes to turn red. If you smoke a second time, the drops are still in there, and continue to work.

Some people have naturally red eyes (or capillaries closer to the skin), that allows for the drops to be absorbed more easily pre-toke, and allows the drop to continue to work after you smoke.

Am I just talking out of my ass, or did that make sense?